Non steroidal anti-inflammatory drugs (NSAIDs) are characterized by a well recognized chemopreventive activity against colorectal cancer (CRC)1,2. This activity has been observed in general population as well as in patients exhibiting an increased risk to develop the mentioned disease. Unfortunately the systemic and gastrointestinal toxicity of NSAIDs drastically limit their administration in the context of clinical protocols requiring a long term treatment of the involved patients. Both therapeutic and toxic effects elicited by these compounds are largely dependent on the inhibition of COX-1 and COX-2 enzymes that, in turn, is responsible for a reduced synthesis of prostaglandins (PG) normally mediating a number of biological functions. It is therefore possible to state that the pharmacological properties of NSAIDs substantially reside in their capacity to interfere with such functions. Several reports indicate that mesalazine (5 aminosalicylic acid or 5-ASA) can be a promising alternative to achieve a comparable anti-CRC chemopreventive activity, avoiding at the same time the side effects induced by NSAIDs3-5. In fact, in spite of the chemical similarity with aspirin, i.e a paradigmatic NSAID, 5-ASA is characterized by a weak COX inhibitory activity, a feature that clearly accounts for the clinical safeness of this therapeutic agent. Not surprisingly distinct mechanisms appear to mediate the anti-inflammatory effect of 5-ASA and, among them, an important role is probably played by the inhibition of transcription factors promoting the immune response such as NFkB and PPARs6. It has to be pointed out that the chemopreventive efficacy of 5-ASA has been, to date, exclusively demonstrated in patients affected by Inflammatory Bowel Diseases (IBD) (Crohn Disease and Ulcerative Colitis), characterized by an increased risk to develop CRC, and it remains to be confirmed in other individual categories such as healthy people or patients carrying genetic tumor syndromes. Although this issue can be univocally addressed through specifically designed clinical trials that could help to clarify the feasibility of anti-CRC chemoprevention with 5-ASA, an adequate characterization of the anti-tumor effects that this compound exerts at the cellular and molecular level could provide a fundamental contribute to such studies. The results of this investigation, in fact, could corroborate the biological rationale of clinical protocols analyzing the chemopreventive efficacy 5-ASA and allow the identification of biological markers able to monitor the pharmacological response to the considered treatment. In this regard, a growing body of evidence indicates that stimulation with 5-ASA determines a number of biological effects on colon cancer cells such as inhibition of proliferation, induction of apoptosis and enhancement of cell cycle checkpoints and DNA repair processes7-10. Interestingly 5-ASA has been recently demonstrated to interfere with the β-catenin signalling pathway by inhibiting the nuclear translocation of β-catenin, necessary to allow the transcription activity of this protein11. This observation could, in principle, explain virtually all the effects that 5-ASA induces on colon cancer cells since β-catenin has been implicated in the molecular control of G1/S12,13 and G2/M14,15 cell cycle transitions and indirectly also of apoptosis. In this patent we present the results of a set of experiments performed on the CaCo2 CRC cell line and aimed to better characterize the molecular mechanisms by which 5-ASA inhibits the β-catenin signalling pathway. The results obtained clearly demonstrated that this effect is at least in part mediated by the induction of a protein called μ-protocadherin that belongs to the cadherin superfamily and is able to sequester β-catenin on plasmatic membrane of 5-ASA treated CRC cells.